Developmental acquisition of genome-wide DNA methylation occurs prior to meiosis in male germ cells
Developmental acquisition of genome-wide DNA methylation occurs prior to meiosis in male germ cells
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DOI：
10.1016/j.ydbio.2007.05.002
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发表时间：
2007-07-15
影响因子：
2.7
通讯作者：
Trasler, J. M.
中科院分区：
文献类型：
--
作者：
Oakes, C. C.;La Salle, S.;Trasler, J. M.
生殖细胞的发育是一个高度有序的过程，在胎儿生长期间开始，并在成人中完成。发生在生殖细胞中的表观遗传修饰对于生殖细胞功能和受精后胚胎发育是重要的。我们先前已经表明，成年小鼠的雄性生殖细胞具有高度独特的表观遗传状态，这是由DNA甲基化的独特全基因组模式所揭示的。虽然已知这些模式开始在胎儿期建立，但不知道精子发生期间DNA甲基化修饰到何种程度。我们使用限制性标记基因组扫描（RLGS）和其他技术来检查小鼠出生后生殖细胞发育过程中基因组多个位点的DNA甲基化。尽管在A型精原细胞阶段之前获得了显著比例的不同生殖细胞模式，但我们发现在精子发生过程中，主要在精原细胞和精母细胞的早期减数分裂前期I中发生了从头甲基化和去甲基化。改变主要包括来自独特基因座和重复元件的非CpG岛序列。这些修饰是渐进的，几乎完全在粗线期精母细胞阶段结束时完成。这些研究更好地定义了男性生殖细胞发育过程中全基因组DNA甲基化模式获得的发育时间。(c)2007年爱思唯尔公司All rights reserved.
The development of germ cells is a highly ordered process that begins during fetal growth and is completed in the adult. Epigenetic modifications that occur in germ cells are important for germ cell function and for post-fertilization embryonic development. We have previously shown that male germ cells in the adult mouse have a highly distinct epigenetic state, as revealed by a unique genome-wide pattern of DNA methylation. Although it is known that these patterns begin to be established during fetal life, it is not known to what extent DNA methylation is modified during spermatogenesis. We have used restriction landmark genomic scanning (RLGS) and other techniques to examine DNA methylation at multiple sites across the genome during postnatal germ cell development in the mouse. Although a significant proportion of the distinct germ cell pattern is acquired prior to the type A spermatogonial stage, we find that both de novo methylation and demethylation occur during spermatogenesis, mainly in spermatogonia and spermatocytes in early meiotic prophase I. Alterations include predominantly non-CpG island sequences from both unique loci and repetitive elements. These modifications are progressive and are almost exclusively completed by the end of the pachytene spermatocyte stage. These studies better define the developmental timing of genome-wide DNA methylation pattern acquisition during male germ cell development. (c) 2007 Elsevier Inc. All rights reserved.